Lithium Hydroxide → 6-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid

HRID 1689788ノート

反応式

HRID 1689788 の反応式
[OH-].[Li+].C[O:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH2:21][CH2:20][CH:19]([O:22][CH2:23][C:24]4[C:25]([C:32]5[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=5[Cl:39])=[N:26][O:27][C:28]=4[CH:29]([CH3:31])[CH3:30])[CH2:18][CH2:17]3)=[CH:13][CH:14]=2)[N:9]([CH3:40])[CH:8]=1)=[O:6]>O1CCOCC1>[Cl:39][C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([Cl:38])[C:32]=1[C:25]1[C:24]([CH2:23][O:22][CH:19]2[CH2:18][CH2:17][N:16]([C:12]3[CH:11]=[C:10]4[C:15]([C:7]([C:5]([OH:6])=[O:4])=[CH:8][N:9]4[CH3:40])=[CH:14][CH:13]=3)[CH2:21][CH2:20]2)=[C:28]([CH:29]([CH3:31])[CH3:30])[O:27][N:26]=1

参加物

4

反応物 2

HCID 3939Lithium HydroxideHCID 593693356-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester

生成物 1

HCID 252049036-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid収率 86%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

A solution of 2N lithium hydroxide (0.9 mL, 5 equiv, 1.8 mmole) is added to a solution of 6-{4-[3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester (200 mg, 1.00 equiv, 0.36 mmole) in 1,4-dioxane (4 mL). The mixture is stirred at 90° C. for 24 h. The organic solvent is removed, HCl (1M) is added to adjust the pH to 3-4, and the resulting aqueous solution is extracted with dichloromethane. The organic layers are combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified via flash chromatography (12 g silica) eluting with a gradient of ethyl acetate in hexane (10% to 100%) to provide the title compound as a pale brown solid (168 mg, 86%). ES/MS m/z 542.0 (M+1).

後処理

  1. customThe organic solvent is removed
  2. additionHCl (1M) is added
  3. extractionthe resulting aqueous solution is extracted with dichloromethane
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified via flash chromatography (12 g silica)
  8. washeluting with a gradient of ethyl acetate in hexane (10% to 100%)

出典と根拠

ORDレコード
ord-33f61b23b34247c28448dc2f5b78e32a
出典データセット
uspto-grants-2012_04
特許番号
US08153624B2

反応ノート

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